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Author Notes:

Correspondence: Scott E. Hemby, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329; Email: shemby@pharm.emory.edu

Acknowledgments: We thank Mr. J. Le and Dr. S. Che for technical assistance and the staff of the Center for Neurodegenerative Disease Research and the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, for assistance in case accrual and evaluation.

We also express our appreciation to the families of the patients studied, who made this research possible.

Disclosures: J.Q.T. is a Founding Scientist and consultant for Layton Biosciences, which has licensed the aRNA amplification and in situ transcription methodologies from the University of Pennsylvania, where J.Q.T. is a faculty member.

Subjects:

Research Funding:

Grant sponsor: National of Institute of Health; Grant number: DA013772; Grant number: NS043939; Grant number: AG10668; Grant number: AG09215; Grant number: AG10124; Grant sponsor: Stanley Foundation; Grant sponsor: Alliance for Autism Research; Grant sponsor: Alzheimer’s Association; Grant number: NIRG-00-2250.

Keywords:

  • aging
  • hippocampus
  • entorhinal cortex
  • gene expression
  • microarray

Neuron-specific age-related decreases in dopamine receptor subtype mRNAs

Tools:

Journal Title:

Journal of Comparative Neurology

Volume:

Volume 456, Number 2

Publisher:

, Pages 176-183

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Age-related decline in dopamine receptor levels has been observed in regional studies of animal and human brains; however, identifying specific cellular substrates and/or alterations in distinct neuronal populations remains elusive. To evaluate whether age-related decreases in dopamine receptor subtypes are associated with specific cell populations in the hippocampus and entorhinal cortex, antisense RNA amplification was combined with cDNA array analysis to examine effects of aging on D1–D5 dopamine receptor mRNA expression levels in hippocampal CA1 pyramidal neurons and entorhinal cortex layer II stellate cells from post-mortem human brains (19–92 years). In CA1 pyramidal neurons, significant age-related decline was observed for dopamine receptor mRNAs (D1–D4, P < 0.001; D5, P < 0.05) but not for the cytoskeletal elements β-actin, three-repeat (3R) tau, and four-repeat (4R) tau. In contrast, no significant changes were observed in stellate cells across the same cohort. Thus, senescence may be a factor responsible for cell-specific decrements in dopamine receptor gene expression in one population of neurons within a circuit that is critical for learning and memory. Furthermore, these results support the hypothesis that alterations in dopaminergic function may also be related to behavioral abnormalities, such as psychosis, that occur with aging.

Copyright information:

© 2002 Wiley-Liss, Inc.

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